Pharmacokinetic-pharmacodynamic analysis of ciprofloxacin in elderly Chinese patients with lower respiratory tract infections caused by Gram-negative bacteria

BACKGROUND: Ciprofloxacin is usually used in the treatment of lower respiratory tract infections (LRTIs). Recent studies abroad have shown ciprofloxacin is inadequately dosed and might lead to worse outcomes. The aim of this study was to perform pharmacokinetic and pharmacodynamic analyses of ciprofloxacin in elderly Chinese patients with severe LRTIs caused by Gram-negative bacteria. METHODS: From September 2012 to June 2014, as many as 33 patients were empirically administered beta-lactam and ciprofloxacin combination therapy. Patients were infused with 200 or 400 mg of ciprofloxacin every 12 h, which was determined empirically by the attending physician based on the severity of the LRTI and the patient's renal condition. Ciprofloxacin serum concentrations were determined by high-performance liquid chromatography. Bacterial culture was performed from sputum samples and/or endotracheal aspirates, and the minimum inhibitory concentrations (MICs) of ciprofloxacin were determined. The ratios of the area under the serum concentration-time curve to the MIC (AUC/MIC) and of the maximum serum concentration of the drug to the MIC (C(max)/MIC) were calculated. The baseline data and pharmacokinetic parameters were compared between clinical success group and clinical failure group, bacteriologic success group and bacteriologic failure group. RESULTS: Among the 33 patients enrolled in the study, 17 were infected with Pseudomonas aeruginosa, 14 were infected with Acinetobacter baumannii, and two were infected with Klebsiella pneumoniae. The mean age of the patients was 76.9 ± 6.7 years. Thirty-one patients (93.4%) did not reach the target AUC/MIC value of >125, and 29 patients (87.9%) did not reach the target C(max)/MIC value of >8. The AUC/MIC and C(max)/MIC ratios in the clinical success group were significantly higher than those in the clinical failure group (61.1 [31.7–214.9] vs. 10.4 [3.8–66.1], Z = −4.157; 9.6 [4.2–17.8] vs. 1.3 [0.4–4.7], Z = −4.018; both P < 0.001). The AUC/MIC and C(max)/MIC ratios in the patients for whom the pathogens were eradicated were significantly higher than those in the patients without the pathogens eradicated (75.3 [31.7–214.9] vs. 10.5 [3.8–66.1], Z = −3.938; 11.4 [4.2–17.8] vs. 1.4 [0.4–5.4], Z = −3.793; P < 0.001 for both). Receiver operating characteristic curve analysis showed that the AUC/MIC and C(max)/MIC values were closely associated with clinical and bacteriologic efficacies (P < 0.001 in both). CONCLUSIONS: Ciprofloxacin is inadequately dosed against Gram-negative bacteria, especially for those with relatively high MIC values. Consequently, the target values, AUC/MIC > 125 and C(max)/MIC > 8, cannot be reached.